The present invention relates to an improved process for preparing 2-halogenoindan-1-ones.
It is already known that, starting from 1-indan-1-ones, indanones which are halogenated in the xcex1 position to the keto group can be prepared by halogenation with elemental chlorine or bromine. This, however, requires the prior synthesis of the corresponding indanone system. This is difficult, in particular if the aromatic moiety of the molecule contains deactivating substituents such as, for example, NO2, Cl, Br, acetyl, etc. It is only then possible to carry out the halogenation (see, for example, J. Org. Chem. 24, 843 (1959) and DE-A 26 40 358). These halogenations are not particularly selective, since they also give rise to polyhalogenated derivatives which then have to be removed in a complicated manner.
Indan-1-ones themselves can be prepared by Friedel-Crafts reactions from the corresponding dihydrocinnamic acids (see, for example, Organ. React., Volume II, Chapter 4). Such cinnamic acids are difficult to obtain, in particular when they contain, for example, halogeno or trifluoromethyl substituents. Particularly disadvantageous are the fact that the aldehyde precursors are sometimes to difficult to obtain, the low yields and the separate halogenation step.
The route for preparing 5-chloroindan-1-ones starting from 3-chloro-1-(4-chlorophenyl)-1-propanone is described in Bull. Soc. Chim. (1973), 11, 3096. Here, however, great amounts of an aluminium trichloride/sodium chloride mixture and high temperatures of, for example, 180xc2x0 C. are required to achieve cyclization. According to WO 96/20151, the same starting material is cyclized using concentrated sulphuric acid; however, this requires highly diluted solutions to be used, which renders work-up difficult and is therefore rather uneconomical. Both processes only yield 5-chloroindan-1-ones which, in order to obtain 2-halogenoindan-1-ones, have to be further halogenated in a subsequent step.
A process for preparing 2-halogenoindan-1-ones of the formula 
in which
X represents hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl or methoxy and
Hal represents chlorine or bromine
has now been found which is characterized in that an aniline of the formula 
in which
X is as defined under formula (I)
is converted into the corresponding diazonium salt of the formula (III) 
in which
X and Hal are as defined under formula (I),
this salt is reacted with an acrylic compound of the formula (IV) 
in which
Y represents COR where Rxe2x95x90OH, Cl, Br, OC1-C4-alkyl or CN,
thus giving a compound of the formula (V) 
in which
X and Hal are as defined under formula (I) and
Y is as defined under formula (IV),
compounds of the formula (V) are then, if required, converted into compounds of the formula (V)xe2x80x2
in which
X and Hal are as defined under formula (I) and
Yxe2x80x2 represents COOH, COCl or COBr,
and a compound of the formula (V)xe2x80x2 is cyclized to a 2-halogenoindan-1-one of the formula (I).
In the formulae,
X preferably represents chlorine, bromine or trifluoromethyl,
Hal preferably represents chlorine,
Y preferably represents COOH, COOC1-C4-alkyl or CN and
Yxe2x80x2 preferably represents COOH or COCl.
The reaction of anilines of the formula (II) to diazonium salts of the formula (III) can be carried out according to generally known methods for preparing diazonium salts.
The aniline can, for example, be dissolved in water together with hydrochloric or hydrobromic acid, and this solution is initially admixed, for example, with sodium chloride or bromide, more hydrochloric or hydrobromic acid and water, and, at a controlled temperature (for example from xe2x88x925 to +15xc2x0 C.), a solution of sodium nitrite in water is metered in. This gives, if appropriate after a period of additional stirring, an aqueous solution of a diazonium salt of the formula (III) which can be reacted as such with an acrylic compound of the formula (IV).
The reaction of the solution of the diazonium salt of the formula (III) with an acrylic compound of the formula (IV) can be carried out, for example, by dissolving the acrylic compound of the formula (IV) in a water-miscible organic solvent, for example acetone, and adding the solution of the diazonium salt to this solution (careful: evolution of gas!). The temperature here can be, for example, from 10 to 60xc2x0 C. It is advantageous to employ an excess of the acrylic compound, for example from 105 to 150% by weight of the amount which is theoretically required. Furthermore, it is advantageous to carry out the reaction in the presence of copper(II) and/or iron(II) salts. To this end, for example, an aqueous solution of copper (II) chloride or bromide or iron(II) chloride can be added to the solution of the acrylic compound of the formula (IV). Per 100 g of acrylic compound of the formula (IV), it is possible to employ, for example, from 2 to 50 g of copper(II) and/or iron(II) salts. This amount is preferably from 3 to 20 g.
If required after a period of additional stirring, the reaction mixture can be worked up, for example, by distilling off the solvent and, if appropriate, any excess acrylic compound which may still be present and admixing the residue with water and then with a water-immiscible solvent, such as diethyl ether, chloroform or toluene. After separation, the compound of the formula (V) produced can be isolated from the organic phase, if appropriate after washing with water, by stripping off the solvent and any acrylic compound of the formula (IV) which may still be present. If desired, the compound of the formula (V) can be purified further, for example by crystallization.
If Y in the compound of the formula (V) present represents COOC1-C6-alkyl or CN, it is now first of all necessary to carry out a conversion into a compound of the formula (V)xe2x80x2 in which Yxe2x80x2 represents COOH, COCl or COBr. It is possible, for example, to obtain from compounds of the formula (V) compounds of the formula (V)xe2x80x2 where Yxe2x80x2xe2x95x90COOH by ester hydrolysis, which is known per se. The latter compounds can, if desired, be converted into compounds of the formula (V)xe2x80x2 where Yxe2x80x2xe2x95x90COCl or COBr by using, for example, an acid halide preparation which is known per se, for example a reaction of a compound of the formula (V) or (V)xe2x80x2 where Y or Yxe2x80x2xe2x95x90COOH with thionyl chloride, phosphorus trichloride or phosphorus tribromide.
For the cyclization step according to the invention for converting a compound of the formula (V)xe2x80x2 to a 2-halogenoindan-1-one, it is possible to use two variants.
1st variant
A compound of the formula (V)xe2x80x2 where Yxe2x80x2xe2x95x90COOH is admixed with a condensing agent and heated. Suitable condensing agents are, for example, polyphosphoric acid, mixtures of polyphosphoric acid and phosphorus pentoxide, methanesulphonic acid, mixtures of methanesulphonic acid and phosphorus pentoxide, sulphuric acid, hydrofluoric acid or trifluoromethanesulphonic acid. The condensing agent is generally employed in excess, for example from 500 to 5000 g, preferably from 600 to 4000 g, of condensing agent per 100 g of the compound of the formula (V)xe2x80x2. The reaction temperature can be, for example, from 25 to 120xc2x0 C., preferably from 30 to 110xc2x0 C. From the reaction mixture which is present after the condensation, it is possible to obtain the 2-halogenoindan-1-one prepared, for example by cooling the reaction mixture, pouring it into ice-water, taking up the organic components in a water-immiscible solvent, for example diethyl ether, chloroform or toluene, drying the organic phase and removing the solvent.
2nd variant
A compound of the formula (V)xe2x80x2 where Yxe2x80x2xe2x95x90COCl or COBr is admixed with a Friedel-Crafts catalyst and heated. Suitable Friedel-Crafts catalysts are, for example, aluminium trichloride, iron trichloride, zinc chloride, aluminium bromide, mixtures thereof and melts of aluminium trichloride/sodium chloride. The Friedel-Crafts catalysts can be employed, for example, suspended in an inert solvent and in amounts of, for example, from 0.9 to 1.3 mol, based on one mole of the compound of the formula (V)xe2x80x2 where Yxe2x80x2xe2x95x90COCl or COBr. Suitable reaction temperatures are, for example, those of from 50 to 100xc2x0 C. Work-up of the reaction mixture can be carried out as for the 1st variant.
The process according to the invention gives, selectively and in good yields, indan-1-ones which are halogenated in the 2 position These can, if required after further finctionalizations, be used as starting material for applications such as those mentioned, for example, in WO 95/29171 and DE-A 26 40 358.
It is surprising that the reversal of the known synthesis route for 2-halogenoindan-1-ones, i.e. carrying out the synthesis, according to the invention, of the indanone skeleton as the last process step, is so much more favourable than the halogenation of indanones, in particular since the synthesis of the indanone skeleton as the last process step in the preparation of 5-halogenoindan-1-ones is not particularly advantageous.
The invention is further described in the following illustrative examples in which all parts and percentages are by weight unless otherwise indicated.